title: Glutamate released spontaneously from astrocytes sets the threshold for synaptic plasticity.
abstract: Astrocytes exhibit spontaneous calcium oscillations that could induce the release of glutamate as gliotransmitter in rat hippocampal slices. However, it is unknown whether this spontaneous release of astrocytic glutamate may contribute to determining the basal neurotransmitter release probability in central synapses. Using whole-cell recordings and Ca(2+) imaging, we investigated the effects of the spontaneous astrocytic activity on neurotransmission and synaptic plasticity at CA3-CA1 hippocampal synapses. We show here that the metabolic gliotoxin fluorocitrate (FC) reduces the amplitude of evoked excitatory postsynaptic currents and increases the paired-pulse facilitation, mainly due to the reduction of the neurotransmitter release probability and the synaptic potency. FC also decreased intracellular Ca(2+) signalling and Ca(2+) -dependent glutamate release from astrocytes. The addition of glutamine rescued the effects of FC over the synaptic potency; however, the probability of neurotransmitter release remained diminished. The blockage of group I metabotropic glutamate receptors mimicked the effects of FC on the frequency of miniature synaptic responses. In the presence of FC, the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N ',N '-tetra-acetate or group I metabotropic glutamate receptor antagonists, the excitatory postsynaptic current potentiation induced by the spike-timing-dependent plasticity protocol was blocked, and it was rescued by delivering a stronger spike-timing-dependent plasticity protocol. Taken together, these results suggest that spontaneous glutamate release from astrocytes contributes to setting the basal probability of neurotransmitter release via metabotropic glutamate receptor activation, which could be operating as a gain control mechanism that regulates the threshold of long-term potentiation. Therefore, endogenous astrocyte activity provides a novel non-neuronal mechanism that could be critical for transferring information in the central nervous system.
authors.affiliation: Departamento de Fisiología, Universidad de Valparaíso, Valparaíso, Chile. christian.bonansco@uv.cl
authors.forename: Christian
authors.initials: C
authors.lastname: Bonansco
authors.forename: Alejandro
authors.initials: A
authors.lastname: Couve
authors.forename: Gertrudis
authors.initials: G
authors.lastname: Perea
authors.forename: Carla Á
authors.initials: CÁ
authors.lastname: Ferradas
authors.forename: Manuel
authors.initials: M
authors.lastname: Roncagliolo
authors.forename: Marco
authors.initials: M
authors.lastname: Fuenzalida
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002951:Citrates / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D002951:Citrates; D018094:Receptors, Metabotropic Glutamate; D005973:Glutamine; C007744:fluorocitrate; D018698:Glutamic Acid; D002118:Calcium